Multifunctional Nanosystem for Targeted and Controlled Delivery of Multiple Chemotherapeutic Agents for the Treatment of Drug-Resistant Breast Cancer

Abstract

By targeting CD44 receptors, inhibiting multidrug resistance (MDR), controlling drug release, and synergistically inhibiting tumor growth, a multilayered nanosystem was developed to serve as a multifunctional platform for the treatment of drug-resistant breast cancers. The multilayer nanosystem is composed of a poly(lactic-co-glycolic acid) core, a liposome second layer, and a chitosan third layer. The chitosan-multilayered nanoparticles (Ch-MLNPs) can co-deliver three chemotherapeutic agents: doxorubicin (DOX), paclitaxel (PTX), and silybin. The three drugs are released from the multilayered NPs in a controlled and sequential manner upon internalization and localization in the cellular endosomes. The presence of a chitosan layer allows the nanosystem to target a well-characterized MDR breast cancer biomarker, the CD44s receptor. In vitro cytotoxicity study showed that the nanosystem loaded with triple drugs, DOX–PTX–silybin, resulted in better antitumor efficacy than the single-drug or dual-drug nano-formulations. Likely attributed to the MDR-inhibition effect of silybin, the co-delivered DOX and PTX exhibited a better synergistic effect on MDR breast cancer cells than on non-MDR breast cancer cells. The in vivo study also showed that the multilayered nanosystem promoted MDR inhibition and synergy between chemotherapeutic agents, leading to significant tumor reduction in a xenograft animal model. Ch-MLNPs reduced the tumor volume by fivefold compared to that of the control group without causing overt cytotoxicity.

RETRACTED: Fabrication, Optimization, and Evaluation of Rotigotine-Loaded Chitosan Nanoparticles for Nose-To-Brain Delivery

“…Furthermore, retaining the drug for a longer period in the nasal cavity using the nanoparticulate systems can enhance the permeability across the epithelial membrane. Over the last decade, polymeric NPs have attracted increasing attention as a drug delivery system due to their biocompatibility, biodegradability, and prolonged half-life in the circulation after intravenous (i.v) administration [11,12,13,14]. More specifically, nanoparticles have been shown to enhance interaction with mucus barriers and protect drugs from biological and/or chemical degradation that may occur during intranasal delivery [10].…”

Increased Level of Mir-204-5p Expression in Melanoma Cells Under the Influence of Dacarbazine

“…Стабильность олигонуклеотидов является одной из ключевых проблем их применения в медицине. Существует множество работ, описывающих проблемы и решение вопросов адресной доставки лекарственных веществ [13,14]. Выделяют несколько направлений решения, включая в случае опухолей кожи, регионарное введение препарата, а также введение препарата посредством различных решений: связывания с полимером, наночастицами, липосомами, вирусными частицами.…”

Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations

“…Based on recent literature [58,59,60,61], we believe that optimizing drug ratios could result in better antitumor efficacy than the single-drug system and each drug significantly changes synergy between the drugs. However, for all of this to be achieved, a better knowledge about the mechanisms of action underlying these drug combinations is required, with a special focus on 5-FU combined with itraconazole, since it was, globally, the most promising drug combination.…”